Angiotensin converting enzyme (ACE) is an enzyme which is chiefly present in the lung, vascular endothelial cells and renal proximal tubules and acts on angiotensin I (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu) (Sequence I) SEQ I to cleave a dipeptide (His.sup.9 -Leu.sup.10) off its C-terminus to give rise to angiotensin II which has potent pressor activity.
Furthermore, this enzyme decomposes bradykinin, a physiological hypotensive substance, to inactivate it and, as such, is intimately involved in the pressor system. It has been considered that inhibition of ACE would lower the blood pressure and is, therefore, clinically useful for the prevention and treatment of hypertension.
Recently, since captopril, a proline derivative, was synthesized and found to have hypotensive activity, much research has been undertaken for synthesizing a variety of ACE inhibitors and it has also been attempted to isolate such substances from natural resources.
This is because natural type ACE inhibitors available from foods or food materials may be expected to be of value as antihypertensive agents of low toxicity and high safety.
However, it is rare that a potent ACE inhibitor is found in natural resources and all that are known at present are teprotide (a nonapeptide, SQ 20881) which was isolated from Brazilian and Japanese snake venoms and Metabolite IS83 of a Streptomyces organism. (Japanese Patent Laid-open No. 58-177920). As ACE inhibitors obtainable by enzymatic treatment of a natural material, the peptides obtainable by hydrolysis of milk casein with trypsin (Japanese Patent Laid-open No. 58-109425, No. 59-44323, No. 59-44324, No. 61-36226 and No. 61-36227) are known. Under the circumstances, development of new, more potent ACE inhibitors has been earnestly awaited.